Continuity mistake: No matter what weapon you are holding before a cut scene appears, the cut scene will always show a pistol, even if you were holding a rifle.
Plot hole: Drake is supposed to be discovering lots of things in the game for the first time, yet every secret door or area he explores, there's always enemies there. If he's supposed to be the first one there, how can the enemies be there before him?
Continuity mistake: The ring that Drake wears around his neck gets left with the body of the deceased Drake. Later on when Drake meets up with Sully, the ring is around his neck again. Then at the end of the game Elena gives the ring to Drake to put around his neck again.
Suggested correction: Elena gives back the ring to Nate at the end.